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研究生:陳柏君
研究生(外文):Puo-Chuan Chen
論文名稱:比較Gd(DTPA-BBA)及Ferumoxide於肝癌之診斷效果
論文名稱(外文):Comparison of Gd(DTPA-BBA) and Ferumoxide for Liver Tumor Detection
指導教授:林永昌林永昌引用關係
學位類別:碩士
校院名稱:國立中興大學
系所名稱:獸醫學系
學門:獸醫學門
學類:獸醫學類
論文種類:學術論文
論文出版年:2001
畢業學年度:89
語文別:中文
中文關鍵詞:肝癌FerumoxideGd(DTPA-BBA)肝臟纖維化
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肝癌患者常併有肝硬化,使用常規的診斷工具很難在肝癌的早期做出確診。許多文獻肯定磁振造影掃瞄診斷肝臟腫瘤的敏感性優於其他影像診斷工具,尤其在配合對比劑的使用後更可診斷出早期的腫瘤。但實際上以肝硬化肝癌動物模式來比較對比劑的研究報告並不多。
因此,本研究以四氯化碳誘導大鼠肝臟纖維化後植入腫瘤的動物模式,比較兩種對比劑:Gd(DTPA-BBA)與Ferumoxide於1.5 Tesla磁振造影掃瞄下T1 WI及T2 WI的診斷效果。在測量影像中的Signal-to-noise ratio(SNR)、relative enhancement(RE)及contrast-to noise ratio(CNR)後,分析與肝臟纖維量、病理學檢查結果之間的關係,並以影像判讀來比較兩種對比劑對腫瘤的偵測率。
結果顯示,以四氯化碳誘導後,肝臟中的纖維量明顯增加。肝組織的SNR在Unenhanced TI WI、Gd-enhanced T1 WI及Fe-enhanced T2 WI 中明顯的下降,Gd- enhanced SNR也不如對照組能在8分鐘內維持一定的增強效果。但其CNR與對照組則無顯著差異。不論是否經四氯化碳誘導,兩種對比劑皆明顯提高對比。迴歸分析的結果顯示Unenhanced T1 SNR、Gd - enhanced CNR及Fe-enhanced CNR皆與肝臟中的纖維量呈負相關。在Fe-enhanced的影像中較少發生誤判,且就腫瘤與肝臟的對比及腫瘤的偵測率上,Ferumoxide效果優於Gd(DTPA-BBA)及Unenhanced影像,也能夠診斷出較小的腫瘤及界定腫瘤的範圍。

Hepatoma usually develops against a background of cirrhosis. Precise diagnosis of tumor growth is difficult in this situation. Among various imaging techniques, magnetic resonance imaging has been proved to be very sensitive for liver tumor detection. By contrast agent administration, higher sensitivity for smaller lesions can be achieved. Although many studies regarding diagnostic efficacy of various MR contrast agents for liver tumors have been reported, few ones are conducted based on animal models of liver fibrosis harboring hepatoma.
This study aims to compare the diagnostic ability of two most frequently used hepatic MR contrast agents, namely, Gadolinium chelates and macrophage monocytic phagocytic system-targeted agent with an animal model of liver fibrosis which simultaneously harbors hepatomas.
Both Gd(DTPA-BBA) and ferumoxide were tested in a GE 1.5 Tesla MR scanner based on T1- and T2-weighted sequences. Various measurements including signal to noise ratio (SNR), relative enhancement (RE), and contrast to noise ratio (CNR) were obtained. The results were correlated with pathological findings and quantitative collagen measurement. Tumor detection rate of these two contrast agents in an environment of fibrotic liver tissue was also compared.
The results showed there was significant increase of collagen in liver tissue after CCl4 induction. The SNR of liver tissue in treated rats was significantly lower than that of control group in unenhanced T1WI, Gd-enhanced T1WI, and Fe-enhanced T2WI.While the SNR of liver tissue was constant in control group within 8 minutes after Gd(DTPA-BBA) enhancement, the treated liver tissue showed dramatic drop after 4 minutes of contrast injection, indicating narrower imaging window for this new T1 agent. The CNR of treated liver, although lower in treated group in all four sequences, was not significantly different from that of control group. After Gd (DTPA-BBA) or ferumoxide enhanced, CNR in both control and treated groups were significantly improved when compared with their unenhanced counterparts. In regression analysis, there was a negative correlation between the fibrous amount and SNR of unenhanced T1WI, CNR of Gd (DTPA-BBA) T1WI, and CNR of ferumoxide-enhanced T2WI. Subjective image reading showed ferumoxide-enhanced T2WI was better than Gd (DTPA-BBA)-enhanced T1WI and other unenhanced sequences for tumor margin delineation and detection of smaller tumors. The false positive culmulative lesions were also much fewer in this sequence.

目 錄
頁次
目錄………………………………………………………….………….Ⅰ
圖次……………………………………………………………….…….Ⅲ
表次……………………………………………………………….…….Ⅲ
中文摘要………………………………………………………….…….Ⅵ
英文摘要………………………………………………………….…….Ⅶ
第一章 前言………………………………………………….…….…1
第二章 文獻探討…………………………………………….…….…3
第一節 肝臟的生理與病理……………………………….….….3
第二節 肝癌的診斷方法……………………………………..….7
第三節 誘導肝纖維化及肝硬化實驗動物模式……………….11
第四節 基本原理……………………………………………….14
第五節 磁振造影掃瞄對肝臟疾病的效應…………………….20
第三章 材料與方法……….……..…..………….……..…..………..25
第一節 實驗動物的前處理… …….……………………………25
第二節 誘導肝臟硬化…… ……………………..……………...25
第三節 實驗動物麻醉………. …………………..……………..26
第四節 腫瘤誘導………..…….… …………………….……….27
第五節 磁振造影掃瞄……………… ……….…………………30
第六節 影像判讀………………………….…………………….32
第七節 病理學檢查………………………….………………….32
第八節 肝臟纖維量分析………………………….…………….32
第四章 結果………………………………………………..…..……37
第一節預備實驗之結果…………...………….………..…………37第二節正式實驗之結果………………………………..………………38
一、 病理學檢查…………………………..……………….38
二、 肝臟膠原纖維纖維含量分析….……..………………39
三、 磁振造影掃瞄………………………..……………….39
四、 影像判讀………………………..…………………….40
第五章 討論………………………..…………………………..……67
第六章 結論………………………..……..……………………..…..77
參考文獻……………………………………………………………..…78
圖 次
頁次
圖1:於大鼠肝臟接種N1S1腫瘤細胞的情形。…...…………….…….35
圖2:大鼠以1.5 Tesla磁振造影儀進行檢查的情形。…………………35
圖3:進行磁振造影掃瞄前,每次定位皆以橫膈為起點,向後每
5 mm取一橫切面。…………………………………………….36
圖4:對照組肝臟外觀。………………………………………………46
圖5:實驗組肝臟觸感堅實,外觀明顯腫大且較為蒼白。……………46
圖6:實驗組肝臟觸感堅實,外觀明顯腫大且較為蒼白。表面有許
多顆粒樣的小結節,呈凹凸不平狀。…………………………47
圖7:接種的腫瘤外圍有結締組織包圍,附近並有血管分佈。
(Masson trichrome,40x)……………………………………47
圖8:腫瘤中心可見到有壞死的情形。(Masson trichrome,40x)…..…48
圖9:腫瘤細胞呈圓形、卵圓形至多角形,大小不一,細胞核
大、核仁明顯,有絲分裂旺盛。(Masson trichrome,200x)……48
圖10:對照組肝臟並無明顯小葉狀構造,只有在血管周圍見到膠原纖維分佈,肝實質中無明顯的纖維分佈(纖維呈淺綠色)。
(Masson trichrome,200x)…….……………………………….49
圖11:實驗組肝臟中可見到大量的膠原纖維分佈已將肝臟實質分
隔成偽小葉狀 (纖維呈淺綠色)。(Masson trichrome,40x)…50
圖12:實驗組肝臟中可見到大量的膠原纖維分佈,部分肝細胞出
現壞死(纖維呈淺綠色)。(Masson trichrome,100x)…………50
圖13:Fiber percentage of control and treated liver tissue……………...51
圖14:對照組MR影像。照片中由左上®右上®左下®右下依序為Gd(DTPA-BBA)-enhanced後2、4、6、8分鐘的影像。…………51
圖15:實驗組MR影像。照片中由左上®右上®左下®右下依序為Gd(DTPA-BBA)-enhanced後2、4、6、8分鐘的影像。…………52
圖16:Gd(DTPA-BBA)-enhanced SNR of liver tissue in differenttime point……………………………………………………………..52
圖17:Gd(DTPA-BBA)-enhanced SNR of tumor in different time point……………………………………………………………..53
圖18:Gd(DTPA-BBA)-enhanced RE of liver tissue in different time point……………………………………………………………..53
圖19:Gd(DTPA-BBA)-enhanced RE of tumor in different time point……………………………………………………………..54
圖20:Gd(DTPA-BBA)-enhanced CNR in different time point……………………………………………………………..54
圖21:Correlation of unenhanced liver T1 SNR and liver fiber percentage. y = -2.01x+57.554 (r = 0.59)………………………………....…57
圖22:Correlation of Gd(DTPA-BBA)-enhanced liver CNR and liver fiber percentage. y = -1.11x+28.993 (r = 0.45)…………...…… 57
圖23:Correlation of Ferumoxide-enhanced CNR and liver fiber
percentage. y = -2.02x+51.766 (r = 0.41)………………..………58
圖24:將肝臟做連續切面後可發現一顆大小約1公分的腫瘤。……59
圖25:在Unenhanced T1影像中,可發現與病理學檢查相同位置
的腫瘤。腫瘤在肝臟中呈低訊號區。…………………………59
圖26:在Unenhanced T2影像中,可發現與病理學檢查相同位置
的腫瘤。腫瘤在肝臟中呈高訊號區。…………………………60
圖27:在Gd(DTPA-BBA)-enhanced T1影像中,可發現與病理學
檢查相同位置的腫瘤。腫瘤在肝臟中呈低訊號區。…………60
圖28:在Ferumoxide-enhanced T2影像中,可發現與病理學檢查
相同位置的腫瘤。腫瘤在肝臟中呈高訊號區。………………61
圖29:將肝臟做連續切面後可發現一顆大小約0.2公分的腫瘤。…62
圖30:在Gd(DTPA-BBA)-enhanced T1影像中,無法明顯見到腫瘤。…………………………………………………. ………….62
圖31:在Ferumoxide-enhanced T2影像中,可發現一顆約0.2公分
的腫瘤。腫瘤在肝臟中呈高訊號區。…………………………63
圖32:將肝臟做連續切面後可發現2顆大小約1.3公分及1.5公分的腫瘤。…………………………………………………………..63
圖33:在Gd(DTPA-BBA)-enhanced T1影像中,可以見到2顆腫瘤。腫瘤在肝臟中呈低訊號區。……………………………………64
圖34:在Ferumoxide-enhanced T2影像中,只見到1顆腫瘤。腫瘤
在肝臟中呈高訊號區。………………………….……………..64
圖35:將肝臟做連續切面後可發現1顆大小約1.2公分的腫瘤。……65
圖36:照片中由左上®右上®左下®右下依序為Unenhanced T1、
Unenhanced T2、Gd(DTPA-BBA)-enhanced及Ferumoxide- enhanced的影像。腫瘤的邊界在Ferumoxide-enhanced T2影像中較清楚。………………………………………………………65
Table
頁次
Table 1 Size and number of tumors.……………………………......49
Table 2 Signal-to-noise ratio of liver tissue……………………...…55
Table 3 Signal-to-noise ratio of tumor…………………………...…55
Table 4 Relative Enhancement of liver tissue………………….…...56
Table 5 Relative Enhancement of tumor………………………..…..56
Table 6 Liver-Tumor contrast-to-noise ratio…………….………….57
Table 7 True-positive localization ratio、true-negtive localization ratio and cumulative false-positive lesion numbers with
each MR sequence……………………………………..…..61
Table 8 Numbers of lesions detected with each MR sequence determine by size of the lesion……………………….…....66

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